Usual Adult Dose for Chronic Hepatitis C

PATIENTS WITHOUT HIV COINFECTION:
Combination Therapy:

• HCV genotypes 1, 2, 3, 4: 180 mcg subcutaneously once a week
• HCV genotypes 5, 6: Insufficient data for dosing recommendations

Duration of therapy when used with other HCV antiviral drugs:

• HCV genotypes 1, 2, 3, 4: The manufacturer product information of the other HCV antiviral drugs should be consulted.

Duration of therapy when used with ribavirin without other HCV antiviral drugs:

• HCV genotypes 1, 4: 48 weeks
• HCV genotypes 2, 3: 24 weeks

Monotherapy: 180 mcg subcutaneously once a week for 48 weeks

Discontinuation of Therapy for HCV Genotype 1 (when used with ribavirin or alone):

• Therapy should be discontinued if there is not at least a 2 log10 reduction from baseline in HCV RNA by 12 weeks of therapy or if HCV RNA remains detectable after 24 weeks of therapy.
• The manufacturer product information for specific coadministered HCV antiviral drugs should be consulted for information on discontinuation based on treatment response.

PATIENTS WITH HIV COINFECTION:
Combination Therapy: 180 mcg subcutaneously once a week

Duration of therapy:

• When used with other HCV antiviral drugs: The manufacturer product information of the other HCV antiviral drugs should be consulted.
• When used with ribavirin without other HCV antiviral drugs: 48 weeks, regardless of HCV genotype

COMMENTS:

• The manufacturer product information for coadministered HCV antiviral drugs should be consulted.
• This drug should not be used alone or in combination with ribavirin without additional HCV antiviral drugs for treatment of chronic hepatitis C (CHC) patients who failed prior interferon alfa therapy.
• This drug is not recommended for treatment of CHC patients who have had solid organ transplantation.
• Therapy should be discontinued at once if hepatic decompensation occurs.

USE: For the treatment of CHC patients (with or without HIV coinfection) with compensated liver disease

• As part of a combination regimen with other HCV antiviral drugs
• As monotherapy if contraindications or significant intolerance to other HCV antiviral drugs

Usual Adult Dose for Chronic Hepatitis B

180 mcg subcutaneously once a week for 48 weeks

Use: For the treatment of patients with HBeAG-positive and HBeAG-negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation

Usual Pediatric Dose for Chronic Hepatitis C

5 years or older: 180 mcg/1.73 m2 x BSA subcutaneously once a week
Maximum dose: 180 mcg

Duration of therapy:

• HCV genotypes 2, 3: 24 weeks
• Other HCV genotypes: 48 weeks

Comments:

• For use with ribavirin
• The manufacturer product information for ribavirin should be consulted.
• Patients who start therapy before their 18th birthday should remain on the recommended pediatric dose until therapy is finished.

Use: In combination with ribavirin, for the treatment of CHC patients with compensated liver disease

Renal Dose Adjustments

Adults:
CrCl less than 30 mL/min: 135 mcg subcutaneously once a week

Comments:

• Signs/symptoms of interferon toxicity should be closely monitored.
• If severe side effects or laboratory abnormalities develop, the dose may be reduced to 90 mcg subcutaneously once a week until the side effects abate. If intolerance persists after dose adjustment, this drug should be discontinued.
• The manufacturer product information for coadministered HCV antiviral drugs should be consulted.

Pediatrics: Data not available

Liver Dose Adjustments

Hepatic decompensation (Child-Pugh B or C [score greater than 6]) in cirrhotic patients: Contraindicated
Hepatic decompensation with Child-Pugh score at least 6 in cirrhotic CHC patients coinfected with HIV: Contraindicated

Dose Modification Due To ALT Elevation in Adults:
If ALT increases are progressive despite dose reduction or accompanied by increased bilirubin or evidence of hepatic decompensation, therapy should be discontinued immediately.

Chronic hepatitis B:

• In patients with ALT elevations (greater than 5 times the upper limit of normal [5 x ULN]), liver function should be monitored more often and either reducing the dose to 135 mcg or temporarily discontinuing therapy should be considered; after dose reduction or withholding, therapy can be resumed after ALT flares subside.
• In patients with persistent, severe (ALT greater than 10 x ULN) hepatitis B flares, therapy discontinuation should be considered.

Chronic hepatitis C:

• In patients with progressive ALT increases above baseline values, the dose should be reduced to 135 mcg and liver function should be monitored more often; after dose reduction or withholding, therapy can be resumed after ALT flares subside.

Dose Modification Due To ALT Elevation in Pediatrics:

• Persistent or increasing ALT elevations 5 to less than 10 x ULN: Dose should be reduced to 135 mcg/1.73 m2 x BSA; weekly monitoring recommended, with further dose reduction if needed, until stable or ALT level decreases.
• Persistent ALT values at least 10 x ULN: Therapy should be discontinued.

Dose Adjustments

ADULTS:
After the side effect, neutropenia, or thrombocytopenia improves, reescalation of the dose back to the previous dose may be considered.

Dose Modification Due To Neutropenia:

• Absolute neutrophil count (ANC) less than 750 cells/mm3: Dose should be reduced to 135 mcg subcutaneously once a week.
• ANC less than 500 cells/mm3: Therapy should be suspended until ANC values return to more than 1000 cells/mm3. Therapy should be restarted at 90 mcg subcutaneously once a week and ANC should be monitored.

Dose Modification Due To Thrombocytopenia:

• Platelet count less than 50,000 cells/mm3: Dose should be reduced to 90 mcg subcutaneously once a week.
• Platelet count less than 25,000 cells/mm3: Therapy should be discontinued.

Dose Modification Due To Depression:

• Mild: No adjustment recommended.
• Moderate: Initial management (4 to 8 weeks) includes reducing dose to 135 mcg subcutaneously once a week; dose reduction to 90 mcg subcutaneously once a week may be required in some cases. Patient should be evaluated once weekly (office visit at least every other week). If symptoms improve and are stable for 4 weeks, recommendations are to continue reduced dosing or return to normal dose.
• Severe: This drug should be permanently discontinued. Psychiatric therapy may be necessary.

PEDIATRICS:
Dose Modification Due To Neutropenia:
ANC 750 to 999 cells/mm3:

• Week 1 to 2: Dose should be reduced to 135 mcg/1.73 m2 x BSA at once.
• Week 3 to 48: No modification.

ANC 500 to 749 cells/mm3:

• Week 1 to 2: Dose should be delayed or held until greater than 750 cells/mm3, then dose should be resumed at 135 mcg/1.73 m2 x BSA. Weekly assessment is recommended for 3 weeks to verify ANC greater than 750 cells/mm3.
• Week 3 to 48: Dose should be reduced to 135 mcg/1.73 m2 x BSA at once.

ANC 250 to 499 cells/mm3:

• Week 1 to 2: Dose should be delayed or held until greater than 750 cells/mm3, then dose should be resumed at 90 mcg/1.73 m2 x BSA.
• Week 3 to 48: Dose should be delayed or held until greater than 750 cells/mm3, then dose should be resumed at 135 mcg/1.73 m2 x BSA.

ANC less than 250 cells/mm3 (or febrile neutropenia): Therapy should be discontinued.

Dose Modification Due To Thrombocytopenia:

• Platelet count less than 50,000 cells/mm3: Dose should be reduced to 90 mcg/1.73 m2 x BSA.

Dose Modification Due To Depression:

• Mild: No adjustment recommended.
• Moderate: Initial management (4 to 8 weeks) includes reducing dose to 135 mcg/1.73 m2 x BSA subcutaneously once a week; dose reduction to 90 mcg/1.73 m2 x BSA subcutaneously once a week may be required in some cases. Patient should be evaluated once weekly (office visit at least every other week). If symptoms improve and are stable for 4 weeks, recommendations are to continue reduced dosing or return to normal dose.
• Severe: This drug should be permanently discontinued. Psychiatric therapy may be necessary.

Precautions

US BOXED WARNING:

• RISK OF SERIOUS DISORDERS: Alpha interferons may cause/aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Close monitoring with periodic clinical and laboratory evaluations are recommended. Therapy should be withdrawn in patients with persistently severe or worsening signs/symptoms of these disorders. In most (but not all) cases, these disorders resolve after therapy is stopped.

Safety and efficacy have not been established in patients younger than 5 years; this drug is contraindicated in neonates and infants because it contains benzyl alcohol.

Consult WARNINGS section for additional precautions.

Dialysis

Adults:
CrCl less than 30 mL/min, including patients on hemodialysis: 135 mcg subcutaneously once a week

Comments:

• Signs/symptoms of interferon toxicity should be closely monitored.
• If severe side effects or laboratory abnormalities develop, the dose may be reduced to 90 mcg subcutaneously once a week until the side effects abate. If intolerance persists after dose adjustment, this drug should be discontinued.
• The manufacturer product information for coadministered HCV antiviral drugs should be consulted.

Pediatrics: Data not available

Other Comments

Administration advice:

• Administer dose on the same day of each week and at the same time.
• Administer the subcutaneous injection in the abdomen or thigh (different location each time).
• Consult the manufacturer product information regarding missed doses.

Storage requirements:

• Store in refrigerator at 2C to 8C (36F to 46F)
• Do not leave out of the refrigerator for more than 24 hours.
• Do not freeze or shake.
• Protect from light.

Preparation techniques:

• The manufacturer product information should be consulted.

General:

• For combination therapy: The manufacturer product information for coadministered HCV antiviral drugs should be consulted.

Monitoring:

• Cardiovascular: ECG for patients with preexisting cardiac disease (before combination therapy)
• General: Standard biochemical laboratory tests (before therapy, at 4 weeks, and periodically during therapy); HCV RNA (periodically during therapy); signs/symptoms of interferon toxicity or other serious side effects
• Hematologic: Standard hematological laboratory tests (before therapy, at 2 and 4 weeks, and periodically during therapy); CBC (before and routinely during therapy)
• Hepatic: Clinical status and hepatic function (during therapy; more often if ALT flares)
• Ocular: Eye examination in all patients (at baseline); ophthalmologic exams in patients with preexisting ophthalmologic disorders (periodically during therapy)
• Psychiatric: Signs/symptoms of depression and other psychiatric symptoms
• Renal: Renal function in all patients by estimating CrCl (before therapy); CrCl in patients with renal dysfunction

Patient advice:

• Keep well hydrated, especially during initial stages of therapy.
• Consult healthcare provider if full dose is not received (e.g., leakage around injection site).